Effects of prolonged administration of lovastatin, an inhibitor of cholesterol synthesis, on the morphology and function of rat Leydig cells.
We examined the effects of a prolonged treatment with lovastatin, a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on the morphology and function of rat Leydig cells. Twenty-four h after the first lovastatin injection, no conspicuous ultrastructural changes were found, but isolated Leydig cells showed a notable reduction in their basal and HCG-stimulated testosterone production. By prolonging lovastatin administration (daily injections for 3 and 5 days), Leydig cells progressively recovered their secretory activity, and this was associated with a striking proliferation of smooth endoplasmic reticulum and peroxisomes. The hypothesis is discussed that these morphologic changes are the counterpart of an enhanced newly synthesis of HMG-CoA reductase, that is the expression of a compensatory response of Leydig cells aimed at maintaining an adequate production of cholesterol (i.e. testosterone precursors) in spite of the chronic competitive inhibition of HMG-CoA reductase by lovastatin.
Andreis
P G
PG
Department of Anatomy, University of Padua, Italy.
Cavallini
L
L
Mazzocchi
G
G
Nussdorfer
G G
GG
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000648:ultrastructure; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000378:metabolism
D000924:Anticholesteremic Agents; D006063:Chorionic Gonadotropin; D013739:Testosterone; D002784:Cholesterol; D008148:Lovastatin